BEBAC  Ing. Helmut Schütz

Point Estimate must include 100%;
Acceptance limits of 90%–111% for narrow therapeutic index drugs

Denmark — DKMA

Dated 17 January 2006 (updated 7 February 2012) the Danish Medicines Agency published a document entiteled ‘Bioequivalence and labelling of medicinal products with regard to generic substitution’.

The Danish Medicines Agency considers that the 90% confidence interval for the ratio test versus reference should include 100% irrespective of whether acceptance limits of 80–125% or narrower are employed. Deviations may be accepted if they can be adequately justified not to have impact on either the overall therapeutic effect or safety profile of the product.

The Danish Medicines Agency also considers that the bioequivalence acceptance limits for immunosuppressives (ATC: L04) must lie within 90–111% as they have a narrow therapeutic index.
For a number of other substances or therapeutic groups, the Danish Medicines Agency considers that authorisation may be granted if the usual acceptance limits (80–125%) are observed, but that therapeutic problems in relation to substitution of the preparations might occur. The bioequivalence limits have therefore been narrowed for such medicinal products when automatic substitution is being considered.